Summary: A good animal model for HIV-1 is essential for AIDS vaccine studies and development of efficacious anti-viral agents. Pig-tailed macaques have been found to be susceptible to HIV-1 infection (Agy, et al., 1992). We have infected pig-tailed macaques with high and low doses of HIV-1/LAI and have been monitoring long-term infection and clinical changes. All of the animals were infected and developed antibodies to both Gag and Env, except in one case where only Env antibodies were seen. Each animal responded uniquely to the infection. Viral sequences and antibody responses have persisted long term. Extensive analysis has been done in 2 of the infected monkeys. In the case of PT86 viral sequences (DNA and RNA) were detected in the PBMC in the first year whereas the lymph nodes were positive even at 3 years post-infection. In the case of PT99 viral DNA sequences were seen in the PBMCs upto 1 year and in the lymph node 3 years PI. Higher Env titers were seen in PT 86 and PT 99 at 3 years post-infection than at 6 years post-infection. Increase in CD8+ T cells correlated with reduced plasma virus load in PT86. Although the CD4+/CD8+ T cell ratio gradually declined in PT86 and was maintained at a lower level, no clinical symptoms have thusfar developed. Since the clinical symptoms of AIDS in humans generally develop in 5-10 years and developed after about 10 years post-infection in one chimpanzee, it is most likely too early to see clinical symptoms in the infected pig-tailed macaques. To evaluate possible suppression of HIV-1 production in infected pig-tailed macaques due to higher levels of CD8+ T cells, the animals will be infused with anti-CD8 antibody and evaluated for HIV-1 plasma viral loads. HIV-1 DNA vaccine (CMV-DNA) produced persistent and boostable Gag and Env humoral repsonses in pig-tailed macaques. The DNA immunized pig-tailed macaques were challenged with homologous virus (HIV-1/LAI). Virus could not be detected in the plasma of CMV-DNA vaccinated animals using bDNA PCR. Studies are underway to investigate the viral sequences in the PBMCs to determine if the DNA vaccinated animals were completely protected against the HIV-1 challenge in the pig-tailed macaque model.